The primary mission of St. Jude Children's Research Hospital is to find cures for children with cancer and other catastrophic diseases through research and treatment. Recent progress at St. Jude has provided a better understanding of the molecular, genetic and chemical bases of cancer in children. These findings have provided new insights into novel targets and treatment modalities for multiple cancers. An extensive therapeutic drug discovery program at St. Jude has identified lead compounds to evaluate in novel preclincial models of childhood cancer. The long-term objective of this application is to support the preclinical development of novel small molecules and their translation to innovative strategies for childhood cancers including acute lymphoblastic leukemia, ependymoma, medulloblastoma, glioma, retinoblastoma and other solid tumors. With the proposed state-of-the-art LC/MS/MS system, the specific aim is to develop, validate and implement sensitive and specific analytical methods for anticancer agents, their metabolites, or other relevant pharmacologic indices in biological samples to facilitate high-quality pharmacokinetic/ pharmacodynamic translational research in pre-clinical models at St. Jude. The proposed equipment will benefit five competitively funded peer-reviewed investigators and their projects through greater assay selectivity, specificity, efficiency, and consistency in application of state-of-the-art equipment and approaches to preclinical pharmacokinetic projects. PUBLIC HEALTH RELEVANCE: Recent progress at St. Jude has provided a better understanding of the molecular, genetic and chemical bases of cancer in children. This project will provide state-of-the-art analytical methods based on mass spectrometry to support the preclinical development of novel small molecules and their translation to innovative therapies for children with cancer.